Variant chr12-8177335-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001004328.3(ZNF705A):c.655G>A(p.Glu219Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000198 in 1,611,804 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00014 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00020 ( 0 hom. )

Consequence

ZNF705A
NM_001004328.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -2.18

Variant links:

Genes affected

ZNF705A (HGNC:32281): (zinc finger protein 705A) Predicted to enable DNA-binding transcription repressor activity, RNA polymerase II-specific and RNA polymerase II transcription regulatory region sequence-specific DNA binding activity. Predicted to be involved in negative regulation of transcription by RNA polymerase II. Predicted to be located in nucleus. Predicted to be part of chromatin. [provided by Alliance of Genome Resources, Apr 2022]

ZNF705A links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.04931128).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF705A	NM_001004328.3 linkuse as main transcript	c.655G>A	p.Glu219Lys	missense_variant	6/6	ENST00000396570.8	NP_001004328.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
ZNF705A	ENST00000396570.8 linkuse as main transcript	c.655G>A	p.Glu219Lys	missense_variant	6/6	5	NM_001004328.3	ENSP00000379816	P1
ZNF705A	ENST00000359286.4 linkuse as main transcript	c.655G>A	p.Glu219Lys	missense_variant	5/5	2		ENSP00000352233	P1
ZNF705A	ENST00000610508.4 linkuse as main transcript	c.655G>A	p.Glu219Lys	missense_variant	6/6	5		ENSP00000481663	P1
ZNF705A	ENST00000398526.2 linkuse as main transcript	c.273+150G>A		intron_variant		3		ENSP00000475525

Frequencies

GnomAD3 genomes

AF:

0.000138

AC:

AN:

152190

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000279

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000292

AC:

AN:

239328

Hom.:

AF XY:

0.0000230

AC XY:

AN XY:

130250

show subpopulations

Gnomad AFR exome

AF:

0.0000683

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000466

Gnomad OTH exome

AF:

0.000175

GnomAD4 exome

AF:

0.000204

AC:

298

AN:

1459614

Hom.:

Cov.:

AF XY:

0.000194

AC XY:

141

AN XY:

726112

show subpopulations

Gnomad4 AFR exome

AF:

0.0000300

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000248

Gnomad4 OTH exome

AF:

0.000349

GnomAD4 genome

AF:

0.000138

AC:

AN:

152190

Hom.:

Cov.:

AF XY:

0.0000673

AC XY:

AN XY:

74340

show subpopulations

Gnomad4 AFR

AF:

0.0000483

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000279

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000214

Hom.:

Bravo

AF:

0.000159

ExAC

AF:

0.0000580

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 21, 2023

The c.655G>A (p.E219K) alteration is located in exon 5 (coding exon 5) of the ZNF705A gene. This alteration results from a G to A substitution at nucleotide position 655, causing the glutamic acid (E) at amino acid position 219 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.83

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0048

T;T

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.0022

LIST_S2

Benign

0.78

T;.

M_CAP

Benign

0.0020

MetaRNN

Benign

0.049

T;T

MetaSVM

Benign

-0.93

MutationAssessor

Benign

-0.20

N;N

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.61

PROVEAN

Benign

-0.92

.;N

REVEL

Benign

0.015

Sift

Benign

0.24

.;T

Sift4G

Benign

0.48

T;T

Polyphen

0.026

B;B

Vest4

0.040

MVP

0.31

MPC

2.6

ClinPred

0.047

GERP RS

-1.4

Varity_R

0.048

gMVP

0.054

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over